Content developed by Suzanne M. Snedeker, Ph.D. Associate Director for Translational Research Cornell University Program on Breast Cancer and Environmental

Content developed byContent developed by

Suzanne M. Snedeker, Ph.D.Suzanne M. Snedeker, Ph.D.

Associate Director Associate Director for Translational Researchfor Translational Research

Cornell UniversityCornell UniversityProgram on Breast Cancer and Program on Breast Cancer and Environmental Risk Factors (BCERF)Environmental Risk Factors (BCERF)

Pieces of the Puzzle:Pieces of the Puzzle: Does Atrazine Affect the Does Atrazine Affect the

Risk of Cancer?Risk of Cancer?

Pieces of the Puzzle: Does Atrazine Affect the Risk of Cancer? Cornell University BCERF, Snedeker 2002Pieces of the Puzzle: Does Atrazine Affect the Risk of Cancer? Cornell University BCERF, Snedeker 2002

• Do environmental chemicals affect the Do environmental chemicals affect the risk of cancer?risk of cancer?

• 1995 Cornell University Program on 1995 Cornell University Program on Breast Cancer and Environmental Risk Breast Cancer and Environmental Risk Factors was founded to address these Factors was founded to address these concernsconcerns

• Launched a new translational research Launched a new translational research programprogram

Translational cancer researchTranslational cancer research– expanding your knowledge– expanding your knowledge


• Address the relationships between Address the relationships between environmental factors and cancer riskenvironmental factors and cancer risk

Translational cancer researchTranslational cancer research– expanding your knowledge – expanding your knowledge



• Critically evaluate the current Critically evaluate the current scientific evidencescientific evidence





• Translate this science-based data into Translate this science-based data into information individuals can use to expand information individuals can use to expand their knowledge and reduce their risk of their knowledge and reduce their risk of cancercancer





• Translate this science-based data into Translate this science-based data into information individuals can use to expand information individuals can use to expand their knowledge and reduce their risk of their knowledge and reduce their risk of cancercancer

• Recommend promising avenues of new Recommend promising avenues of new researchresearch



Breast cancer statistics for the USBreast cancer statistics for the US– projections for the year 2002– projections for the year 2002

New Cases in Women: New Cases in Women: 203,500203,500

New Cases in Men: New Cases in Men: 1,5001,500

* US estimates for 2002 from the American Cancer Society, * US estimates for 2002 from the American Cancer Society, Cancer Facts & Figures 2002Cancer Facts & Figures 2002


The puzzle of breast cancerThe puzzle of breast cancer

• Very complex diseaseVery complex disease


• Very complex diseaseVery complex disease• No one single factor associated No one single factor associated

with causing the diseasewith causing the disease



• Very complex diseaseVery complex disease• No one single factor associated No one single factor associated

with causing the diseasewith causing the disease• Breast cancer develops over a Breast cancer develops over a

long period of time, usually 10 to long period of time, usually 10 to 30 years30 years



The puzzle of breast cancerThe puzzle of breast cancer– – how does breast cancer occur?how does breast cancer occur?

• There are many stepsThere are many steps


The puzzle of breast cancer The puzzle of breast cancer – – how does breast cancer occur?how does breast cancer occur?

• There are many stepsThere are many steps• Occurs as a result of a cell Occurs as a result of a cell

accumulating changes in key accumulating changes in key genes that control the cell’s genes that control the cell’s ability to divide, mature and dieability to divide, mature and die



• There are many stepsThere are many steps• Occurs as a result of a cell Occurs as a result of a cell

accumulating changes in key accumulating changes in key genes that control the cell’s genes that control the cell’s ability to divide, mature and dieability to divide, mature and die

• The result is an abnormal cell The result is an abnormal cell that divides out of control and that divides out of control and forms a tumorforms a tumor



• As the tumor grows, it may As the tumor grows, it may invade surrounding or distant invade surrounding or distant tissuestissues

• Cancer cells can break off Cancer cells can break off from the primary tumor and from the primary tumor and travel to distant sites invading travel to distant sites invading vital organsvital organs

• EarlyEarly detection is important


Risks related to breast cancerRisks related to breast cancer






PesticidesPesticides– – potential for exposurepotential for exposure

CroplandCropland GardensGardens

RecreationRecreation Insect ControlInsect Control


Pesticides and breast cancer riskPesticides and breast cancer risk– – possible mechanismspossible mechanisms

• ““Complete” carcinogenComplete” carcinogen



• ““Complete” carcinogenComplete” carcinogen• Co-carcinogen / tumor promoterCo-carcinogen / tumor promoter


• Endocrine disruptor Endocrine disruptor (Hormonally Active Agent)(Hormonally Active Agent)

– Mimics other hormonesMimics other hormones– Affects formation or breakdown of Affects formation or breakdown of

other hormonesother hormones– Supports the growth of a hormone-Supports the growth of a hormone-

dependent tumordependent tumor– EPA is developing tests to identify EPA is developing tests to identify

which pesticides are endocrine which pesticides are endocrine disruptorsdisruptors



AtrazineAtrazine



Most widely used herbicide in the USMost widely used herbicide in the US• First registered for use in 1959First registered for use in 1959• Annual crop land usage Annual crop land usage – Up to 77.3 million lbs active ingredient*Up to 77.3 million lbs active ingredient*

**Source: Asplein, 1999Source: Asplein, 1999

AtrazineAtrazine– – usageusage



Agricultural cropsAgricultural crops

• Primary crops Primary crops – Field and sweet corn, sorghum and Field and sweet corn, sorghum and

sugarcanesugarcane



Agricultural cropsAgricultural crops• Primary crops Primary crops – Field and sweet corn, sorghum and Field and sweet corn, sorghum and

sugarcane sugarcane • Other crops Other crops – Winter wheat, guava and macadamia Winter wheat, guava and macadamia

nutsnuts– Hay for animal fodderHay for animal fodder– Fallow landFallow land– Christmas tree farmsChristmas tree farms


Other weed control usesOther weed control uses• Turf – golf courses, home lawn careTurf – golf courses, home lawn care

(Southeastern US, St. Augustine and (Southeastern US, St. Augustine and Bermuda grass)Bermuda grass)

• Right-of-waysRight-of-ways



Application rates varyApplication rates vary– Field corn, 1 lb to 2.5 lbs per acreField corn, 1 lb to 2.5 lbs per acre– Sugarcane, up to 10 lbs per acreSugarcane, up to 10 lbs per acre– Turf*, 2.0 lbs or less per acreTurf*, 2.0 lbs or less per acre

(* Southeastern US)(* Southeastern US)



Atrazine Atrazine – cancer risk in women– cancer risk in women

Breast cancerBreast cancer Two “ecological” studies from KentuckyTwo “ecological” studies from Kentucky• Study #1: higher rate of breast cancer in Study #1: higher rate of breast cancer in

counties with:counties with:– Higher use of corn herbicidesHigher use of corn herbicides– Higher levels of triazine herbicides in Higher levels of triazine herbicides in

water supplieswater supplies– Study criticized because of crude Study criticized because of crude

methods used to estimate atrazine methods used to estimate atrazine exposuresexposures



Breast cancerBreast cancer Two “ecological” studies from KentuckyTwo “ecological” studies from Kentucky• Study #2, a 5-year follow-up study: Study #2, a 5-year follow-up study: – Breast cancer risk Breast cancer risk notnot associated with associated with

• Acres of corn planted Acres of corn planted • Atrazine sales Atrazine sales • Atrazine levels in water suppliesAtrazine levels in water supplies

– But, study did not measure skin But, study did not measure skin exposures, drift, or levels inside farm exposures, drift, or levels inside farm homeshomes


Atrazine Atrazine – cancer risk in lab animals– cancer risk in lab animals

Breast CancerBreast Cancer• Increased number or earlier appearance Increased number or earlier appearance

of mammary (breast) tumors in one type of mammary (breast) tumors in one type of female ratof female rat

• Not all types of laboratory animals are Not all types of laboratory animals are affectedaffected

• No mammary tumors seen in other rat No mammary tumors seen in other rat strains or in mice fed atrazinestrains or in mice fed atrazine


Breast CancerBreast Cancer• Atrazine is not an estrogen mimicAtrazine is not an estrogen mimic• May disrupt other hormonal pathways May disrupt other hormonal pathways

that affect mammary cancer that affect mammary cancer in ratsin rats– Decreases luteinizing hormoneDecreases luteinizing hormone– Increases prolactin levelsIncreases prolactin levels



Breast CancerBreast Cancer• Atrazine is not an estrogen mimicAtrazine is not an estrogen mimic• May disrupt other hormonal pathways May disrupt other hormonal pathways

that affect mammary cancer that affect mammary cancer in ratsin rats– Decreases luteinizing hormoneDecreases luteinizing hormone– Increases prolactin levelsIncreases prolactin levels

• These two hormonal pathways may not These two hormonal pathways may not be as important in human breast cancerbe as important in human breast cancer




Ovarian cancerOvarian cancer• Study of Italian women Study of Italian women • Exposed to triazine herbicides Exposed to triazine herbicides – Atrazine and simazineAtrazine and simazine

• Risk of ovarian cancer higher in Risk of ovarian cancer higher in exposed womenexposed women


Stomach cancerStomach cancer• Emerging area of researchEmerging area of research• Study in Ontario, CanadaStudy in Ontario, Canada– Higher rates of stomach Higher rates of stomach

cancer seen in areas with cancer seen in areas with higher levels of atrazine in higher levels of atrazine in the drinking waterthe drinking water

Atrazine Atrazine – cancer risk in men– cancer risk in men


Atrazine Atrazine – cancer risk in men– cancer risk in men

Non-Hodgkin’s lymphoma (NHL)Non-Hodgkin’s lymphoma (NHL)• Inconsistent results in studies of Inconsistent results in studies of

Midwestern male farmers Midwestern male farmers – Studies in Iowa, Minnesota, and Ontario, Studies in Iowa, Minnesota, and Ontario,

Canada did not see a higher risk of NHL Canada did not see a higher risk of NHL – Studies in Nebraska and Kansas saw higher Studies in Nebraska and Kansas saw higher

risk of NHLrisk of NHL– When they controlled for other pesticides (e.g. When they controlled for other pesticides (e.g.

2,4-D), atrazine-effect not as strong2,4-D), atrazine-effect not as strong


AtrazineAtrazine – – EPA’s cancer risk assessmentEPA’s cancer risk assessment

• 19881988– EPA rated atrazine as a ‘possible EPA rated atrazine as a ‘possible

human carcinogen’ human carcinogen’ • 1994 to present1994 to present– EPA placed atrazine under “Special EPA placed atrazine under “Special

Review” Review” • December 1999 December 1999 – EPA’s preliminary cancer risk EPA’s preliminary cancer risk

assessment, rated as ‘probable human assessment, rated as ‘probable human carcinogen’carcinogen’

19881988

19941994

19991999

20022002

20012001

20002000


• 20002000– Scientific Advisory Panel (SAP) did Scientific Advisory Panel (SAP) did

not agree with EPA draft reportnot agree with EPA draft report– New research on relevancy of rat data New research on relevancy of rat data

availableavailable– Atrazine caused reproductive changes Atrazine caused reproductive changes

in one strain of rats that influenced in one strain of rats that influenced levels of hormones important in rat levels of hormones important in rat mammary (breast) cancer mammary (breast) cancer


19881988

19941994

19991999

20022002

20012001

20002000


• 2000 (continued)2000 (continued)– These reproductive changes seen in These reproductive changes seen in

atrazine-treated rats probably would atrazine-treated rats probably would not occur in womennot occur in women

– SAP concluded that it is unlikely that SAP concluded that it is unlikely that atrazine would affect human breast atrazine would affect human breast cancer riskcancer risk


19881988

19941994

19991999

20022002

20012001

20002000


• June 2000 June 2000 – Based on SAP recommendations the Based on SAP recommendations the

EPA changed atrazine’s cancer EPA changed atrazine’s cancer classification to: classification to: “not likely to be a carcinogen in “not likely to be a carcinogen in humans”humans”

• EPA’s reregistration decision expected EPA’s reregistration decision expected in 2003in 2003


19881988

19941994

19991999

20022002

20012001

20002000


Atrazine Atrazine – effects on wildlife– effects on wildlife

• Sexual development in frogsSexual development in frogs• Male tadpoles exposed to atrazine Male tadpoles exposed to atrazine – All had abnormal sexual developmentAll had abnormal sexual development– Up to 20% had both testes and ovariesUp to 20% had both testes and ovaries– Males were more like femalesMales were more like females


• Sexual development in frogsSexual development in frogs• Male tadpoles exposed to atrazine Male tadpoles exposed to atrazine – All had abnormal sexual developmentAll had abnormal sexual development– Up to 20% had both testes and ovariesUp to 20% had both testes and ovaries– Males were more like femalesMales were more like females– Occurred at very low levels of atrazineOccurred at very low levels of atrazine



• Sexual development in frogsSexual development in frogs• Male tadpoles exposed to atrazine Male tadpoles exposed to atrazine – All had abnormal sexual developmentAll had abnormal sexual development– Up to 20% had both testes and ovariesUp to 20% had both testes and ovaries– Males were more like femalesMales were more like females– Occurred at very low levels of atrazineOccurred at very low levels of atrazine– Adult frogs had low levels of the male Adult frogs had low levels of the male

hormone testosteronehormone testosterone



• Sexual development in frogsSexual development in frogs– Atrazine may increase levels of an Atrazine may increase levels of an

enzyme called aromataseenzyme called aromatase– This enzyme converts testosterone to This enzyme converts testosterone to

estrogenestrogen– Would explain why blood levels of Would explain why blood levels of

testosterone in atrazine-treated male testosterone in atrazine-treated male frogs are so lowfrogs are so low

– More research is needed to confirm More research is needed to confirm this “aromatase” hypothesisthis “aromatase” hypothesis



Atrazine Atrazine – effects on aromatase– effects on aromatase

• Are levels of the aromatase enzyme or Are levels of the aromatase enzyme or sex hormones changed in humans sex hormones changed in humans exposed to atrazine? exposed to atrazine? – Not knownNot known


Atrazine Atrazine && its breakdown products its breakdown products– – exposures of concernexposures of concern

• Workplace exposures:Workplace exposures:– Handling, mixing, loading or applying Handling, mixing, loading or applying

to row crops or right-of-waysto row crops or right-of-ways



to row crops or right-of-waysto row crops or right-of-ways– Post-application field work (sugarcane)Post-application field work (sugarcane)




to row crops or right-of-waysto row crops or right-of-ways– Post-application field work (sugarcane)Post-application field work (sugarcane)– Aerial application or hand sprayingAerial application or hand spraying



• Workplace exposures:Workplace exposures:– Turf applicationTurf application• Use of “belly grinders”Use of “belly grinders”• Proper protective clothing is needed Proper protective clothing is needed

when applying atrazine to treat turf when applying atrazine to treat turf in playgrounds, golf courses and in playgrounds, golf courses and residential lawns. residential lawns.



• Rural familiesRural families– Drift from treated fieldsDrift from treated fields



• Rural familiesRural families– Drift from treated fieldsDrift from treated fields– Tracking into homesTracking into homes



• Rural familiesRural families– Drift from treated fieldsDrift from treated fields– Tracking into living & food Tracking into living & food

preparation areaspreparation areas– Handling soiled work clothesHandling soiled work clothes



• Rural familiesRural families– Drift from treated fieldsDrift from treated fields– Tracking into living & food preparation Tracking into living & food preparation

areasareas– Handling soiled work clothesHandling soiled work clothes– Drinking water from contaminated Drinking water from contaminated

wells or contaminated community wells or contaminated community water supplieswater supplies



Atrazine levels in water supplies Atrazine levels in water supplies – trends– trends

1980s1980s• Frequent detectionFrequent detection of atrazine in of atrazine in

groundwater and surface watergroundwater and surface water


1980s1980s• Frequent detectionFrequent detection of atrazine in of atrazine in

groundwater and surface water groundwater and surface water • Levels greater than the EPA ‘Maximum Levels greater than the EPA ‘Maximum

Contaminant Level’ (MCL) of 3 Contaminant Level’ (MCL) of 3 g/Lg/L• Levels detected exceeded 20 Levels detected exceeded 20 g/L g/L



1980s1980s• Surface water levels – influenced by Surface water levels – influenced by

surface run-off from spring rains after surface run-off from spring rains after applicationapplication



1990-2000s1990-2000s• Still see high frequency of detectionStill see high frequency of detection• Now have very sensitive methodsNow have very sensitive methods• Analytical ability to detect atrazine has Analytical ability to detect atrazine has

improved improved • However, However, levels are lowerlevels are lower, , usually below usually below

MCL allowed in drinking water MCL allowed in drinking water

• But, there is concern that in some But, there is concern that in some agricultural areas, still see atrazine levels agricultural areas, still see atrazine levels

exceeding the MCLexceeding the MCL



• Residential - Recreational ExposureResidential - Recreational Exposure• Adults Adults

– Mixing and applying atrazine to turf Mixing and applying atrazine to turf – Contact with treated turf; residential Contact with treated turf; residential

lawns, mowing, golf courses and parkslawns, mowing, golf courses and parks– Tracking into living & food preparation Tracking into living & food preparation

areasareas

• Children Children – Playing on treated turf at home, Playing on treated turf at home,

playgrounds and parksplaygrounds and parks– Hand to mouth behavior, and dirt eatingHand to mouth behavior, and dirt eating



Atrazine and cancer riskAtrazine and cancer risk– the unanswered questions– the unanswered questions

• Is the risk of breast or ovarian cancer Is the risk of breast or ovarian cancer increased in women? increased in women?

• Is the risk of stomach cancer or Non-Is the risk of stomach cancer or Non-Hodgkin’s lymphoma (NHL) increased in Hodgkin’s lymphoma (NHL) increased in men?men?


• Do low levels of atrazine have an impact Do low levels of atrazine have an impact on wildlife ecology and declining on wildlife ecology and declining amphibian populations?amphibian populations?

• Does atrazine increase levels of the Does atrazine increase levels of the aromatase enzyme and affect sex aromatase enzyme and affect sex hormone levels in humans?hormone levels in humans?



• What are the trends in levels of atrazine What are the trends in levels of atrazine and its breakdown products in surface and its breakdown products in surface water, rural drinking water wells and water, rural drinking water wells and rainfall?rainfall?

• Can atrazine breakdown products affect Can atrazine breakdown products affect human health?human health?

• Can exposure to atrazine affect sensitive Can exposure to atrazine affect sensitive populations such as children or populations such as children or developing wildlife?developing wildlife?



Pesticides and health outcomesPesticides and health outcomes– emerging research– emerging research

Agricultural Health StudyAgricultural Health Study• Evaluating whether exposure to Evaluating whether exposure to

agrochemicals affects the health of farm agrochemicals affects the health of farm familiesfamilies

• Ten-year study sponsored by the Ten-year study sponsored by the National Institutes of HealthNational Institutes of Health

• Includes 57,000 men and 32,000 women Includes 57,000 men and 32,000 women from farm families in Iowa and North from farm families in Iowa and North CarolinaCarolina


Pesticides and health outcomesPesticides and health outcomes– emerging research– emerging research

Agricultural Health StudyAgricultural Health Study• Health endpoints to be evaluatedHealth endpoints to be evaluated

– Breast and Prostate CancerBreast and Prostate Cancer– Parkinson’s diseaseParkinson’s disease– Thyroid diseaseThyroid disease– ReproductionReproduction– AsthmaAsthma– OsteoperosisOsteoperosis– Childhood diabetesChildhood diabetes

For more information http://www.aghealth.org/For more information http://www.aghealth.org/


SummarySummary

• Breast cancer is a complex disease and Breast cancer is a complex disease and environmental factors may play a role in environmental factors may play a role in determining its riskdetermining its risk

• Atrazine is widely used in agriculture for crop Atrazine is widely used in agriculture for crop protection especially for corn, sorghum, protection especially for corn, sorghum, sugarcane, and hay crops, and on turf in the sugarcane, and hay crops, and on turf in the Southeastern USSoutheastern US


SummarySummary

• Atrazine causes mammary tumors in some Atrazine causes mammary tumors in some types of laboratory animalstypes of laboratory animals

• We do not have strong evidence that atrazine We do not have strong evidence that atrazine affects the risk of cancer in humansaffects the risk of cancer in humans

• The EPA has concluded atrazine is not a The EPA has concluded atrazine is not a human carcinogenhuman carcinogen

• Low levels of atrazine in water can cause Low levels of atrazine in water can cause harmful effects on the sexual development of harmful effects on the sexual development of frogsfrogs


SummarySummary

• There are exposures of concern to atrazine in There are exposures of concern to atrazine in both workplace and residential settingsboth workplace and residential settings

• Atrazine is widely detected at low levels in Atrazine is widely detected at low levels in water supplies, and there is some concern water supplies, and there is some concern that levels above drinking water standards that levels above drinking water standards persist in some agricultural areaspersist in some agricultural areas

• More research is needed to monitor levels in More research is needed to monitor levels in water supplies, determine human health risks water supplies, determine human health risks including cancer risk, and effects on wildlifeincluding cancer risk, and effects on wildlife


Resources on PesticidesResources on Pesticides – http://envirocancer.cornell.edu– http://envirocancer.cornell.edu

• Cancer mapsCancer maps• Fact sheets on cancer risk and chemicalsFact sheets on cancer risk and chemicals• Bibliographies on environmental risk factorsBibliographies on environmental risk factors• Searchable Bibliographic DatabaseSearchable Bibliographic Database• Newsletter “Newsletter “The Ribbon”The Ribbon”• Links to:Links to:

– Information on health effects of pesticides, Information on health effects of pesticides, policy and legislation, and new research policy and legislation, and new research studiesstudies


BCERF on the WebBCERF on the Web

http://envirocancer.cornell.eduhttp://envirocancer.cornell.edu

BCERF on the WebBCERF on the Web

http://envirocancer.cornell.eduhttp://envirocancer.cornell.edu

Cornell UniversityCornell UniversityProgram on Breast Cancer and Program on Breast Cancer and

Environmental Risk FactorsEnvironmental Risk Factorsin New York State in New York State

(BCERF)(BCERF)


AcknowledgmentsAcknowledgments– funding– funding

This material is based upon work supported by This material is based upon work supported by Smith Lever funds from the Cooperative State Smith Lever funds from the Cooperative State Research, Education, and Extension Service, Research, Education, and Extension Service, US Department of Agriculture and a grant from US Department of Agriculture and a grant from the New York State Departments of Health and the New York State Departments of Health and Environmental Conservation. Environmental Conservation.

Any opinions, findings, conclusions, or Any opinions, findings, conclusions, or recommendations expressed in this module are recommendations expressed in this module are those of the author and do not reflect the view those of the author and do not reflect the view of the grantors.of the grantors.


AcknowledgementsAcknowledgements– production and design– production and design

• Graphics & Animation:Graphics & Animation: - Mari Stewart - Mari Stewart - Sean Gardner - Sean Gardner - Jason Hernandez - Jason Hernandez

• Narration:Narration: - Mari Stewart - Mari Stewart

• Guidebook Formatting: Guidebook Formatting: - Neil Rotach - Neil Rotach - Carin Rundle - Carin Rundle - Mari Stewart - Mari Stewart

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Content developed by Suzanne M. Snedeker, Ph.D. Associate Director for Translational Research Cornell University Program on Breast Cancer and Environmental